Simultaneous large cell neuroendocrine carcinoma and adenocarcinoma of the stomach

A large cell neuroendocrine carcinoma(LCNEC) of the stomach is very rare.A 76-year-old Japanese man was admitted to our hospital because of epigastralgia and nausea.Endoscopy revealed 2 large tumors in the stomach.He did not have multiple endocrine neoplasia typeⅠor Zollinger-Ellison syndrome.Imaging modalities,including computed tomography and magnetic resonance imaging,revealed no other tumors.Gastrectomy,cholecystectomy,and lymph node dissection were performed.The resected stomach had 2 tumors:one was an antral ulcerated type 3 tumor measuring 5 cm x 5 cm,and the other was a polypoid type 1 tumor measuring 6 cm x 6 cm x 3 cm in the fundus.Microscopically,the antral ulcerated tumor was a well differentiated adenocarcinoma with deep invasion.The fundus polypoid tumor was a LCNEC,being composed of malignant large cells arranged in trabecular and nested patterns.The tumor cells were large and the nuclei were vesicular.Nucleoli were frequently present,and there were many mitotic figures,apoptotic bodies,and necrotic areas.Much lymphovascular permeation was seen.Seven out of 29 dissected lymph nodes showed metastatic foci;6 were from the LCNEC and 1 from theadenocarcinoma.Many intravascular tumor emboli of LCNEC were seen in the peritoneum around the lymph nodes.Mucins were present in the adenocarcinoma but not in the LCNEC.Immunohistochemically,the LCNEC tumor cells were positive for pancytokeratins,synaptophysin(50%positive) ,chromogranin A(10% positive) ,Ki-67(90%labeled) ,and platelet-derived growth factor-α(80%positive) .They were negative for KIT,p53,CD56,and neuron-specific enolase.The non-cancerous stomach showed a normal number of endocrine cells.The patient is now treated with adjuvant chemotherapy.

Esophageal combined carcinomas:Immunohoistochemical and molecular genetic studies

Primary esophageal combined carcinoma is very rare.The authors herein report 2 cases.Case 1 was a combined squamous cell carcinoma and small cell carcinoma,and case 2 was a combined squamous cell carcinoma,adenocarcinoma,and small cell carcinoma.Case 1 was a 67-year-old man with complaints of dysphagia.Endoscopic examination revealed an ulcerated tumor in the middle esophagus,and 6 biopsies were obtained.All 6 biopsies revealed a mixture of squamous cell carcinoma and small cell carcinoma.Both elements were positive for cytokeratin,epithelial membrane antigen,and p53 protein,and had high Ki-67 labeling.The small cell carcinoma element was positive for synaptophysin,CD56,KIT,and platelet-derived growth factor-α(PDG-FRA),while the squamous cell carcinoma element was not.Genetically,no mutations of KIT and PDGFRA were recognized.The patient died of systemic carcinomatosis 15 mo after presentation.Case 2 was a 74-year-old man presenting with dysplasia.Endoscopy revealed a polypoid tumor in the distal esophagus.Seven biopsies were taken,and 6 showed a mixture of squamous cell carcinoma,small cell carcinoma,and adenocarcinoma.The 3 elements were positive for cytokeratins,epithelial membrane antigen,and p53 protein,and had high Ki-67 labeling.The adenocarcinoma element was positive for mucins.The small cell carcinoma element was positive for CD56,synaptophysin,KIT,and PDGFRA,but the other elements were not.Mutations of KIT and PDGFRA were not recognized.The patient died of systemic carcinomatosis 7 mo after presentation.These combined carcinomas may arise from enterochromaffin cells or totipotential stem cell in the esophagus or transdifferentiation of one element to another.A review of the literature was performed.